In Silico and Glioblastoma Cell Line Evaluation of Thioflavin-Derived Zinc Nanoparticles Targeting Beclin Protein.

Introduction: This study explores the anticancer potential of Thioflavin-derived zinc nanoparticles (Th-ZnNPs) using both in vitro and in silico methods. Thioflavin, known for its specific binding properties, faces challenges such as bioavailability, rapid metabolism, and solubility. To overcome these limitations and enhance therapeutic efficacy, nanotechnology was utilized to synthesize Th-ZnNPs. These nanoparticles (NPs) are designed to improve drug delivery and effectiveness. The Beclin protein, which plays a critical role in regulating autophagy in cancer cells, was identified as a potential target for these NPs. The study aims to evaluate the interaction between Th-ZnNPs and Beclin protein in glioblastoma cell lines and assess the potential of these NPs as novel anticancer agents.

Methods:  Th-ZnNPs were synthesized using advanced nanotechnology techniques to improve the bioavailability and solubility of Thioflavin. To explore their anticancer potential, in silico analyses were performed, including molecular docking studies to evaluate the binding affinity between the ZnNPs and Beclin protein, which is integral to autophagy regulation. This computational approach identified the Beclin protein as a promising target for the ZnNPs. Complementary in vitro assays were then conducted, where glioblastoma cell lines (procured from the National Centre for Cell Science, Pune, India) were treated with ZnNPs to assess their cytotoxic effects. The assays also included mechanistic studies to validate the interaction between ZnNPs and Beclin protein and to understand their influence on autophagy pathways.

Results: The synthesis of Th-ZnNPs successfully enhanced their solubility and bioavailability compared to Thioflavin alone. In silico findings showed a strong binding affinity between the Th-ZnNPs and the Beclin protein, suggesting that these NPs may effectively target cancer cells through this interaction. Beclin protein was validated as a relevant target due to its critical role in autophagy regulation. In vitro assays further confirmed the anticancer potential of the Th-ZnNPs, as they exhibited significant cytotoxic effects on glioblastoma cells. Additionally, mechanistic studies revealed that Th-ZnNPs impact Beclin protein and modulate autophagy pathways, supporting their proposed role as effective anticancer agents.

Conclusions: The study highlights the promising anticancer potential of Th-ZnNPs. By overcoming the limitations of Thioflavin through nanotechnology, these NPs show significant therapeutic promise in targeting glioblastoma cells. The strong binding affinity between Th-ZnNPs and the Beclin protein, coupled with confirmed cytotoxic effects, underscores their potential as novel anticancer agents. This integrated approach not only enhances the delivery and efficacy of Thioflavin but also opens new avenues for targeted therapy in glioblastoma treatment.